Immunotherapy With Tarlatamab May Improve Responses in Previously Treated SCLC

Tarlatamab was safe and effective in treating patients with small cell lung cancer, study results showed.

Tarlatamab, a form of immunotherapy called a bispecific T-cell engager, contributed to antitumor activity and favorable side effect profiles in patients with previously treated small cell lung cancer (SCLC), recent study results demonstrated.

Findings from the phase 2 DeLLphi-301 study were presented at the European Society for Medical Oncology Congress 2023.

Researchers conducting this study enrolled patients with extensive-stage SCLC whose disease relapsed after at least two prior lines of therapy, including a platinum-based regimen either with or without a checkpoint inhibitor. In part 1 of this study, patients were randomly assigned to receive tarlatamab either at a 10-mg dose (100 patients) or a 100-mg dose (88 patients).

The objective response rate (the percentage of patients who had a complete or partial response to treatment) for patients treated with the 10-mg dose was 40% versus 32% with the 100-mg dose. The rate of patients who responded to tarlatamab for at least six months was 58% in the 10-mg group and 61% in the 100-mg group.

“Tarlatamab has shown manageable safety profile and activity,” Dr. Luis Paz-Ares, chair of the medical oncology department at the Hospital Doce de Octubre, associate professor at the Universidad Complutense, and head of the lung cancer unit at the CNIO in Madrid, Spain, said during the presentation of the data. “We have chosen 10 milligrams to go to further development.”

As Paz-Ares explained, SCLC is an aggressive form of cancer and patients with this malignancy face poor survival outcomes. Specifically, there are no approved therapies in the third-line or beyond. However, tarlatamab showed manageable safety and encouraging efficacy data in a phase 1 study of pretreated patients with SCLC. Paz-Ares expressed optimism about targeting pretreated SCLC with this approach.

“Tarlatamab is a BiTE, bispecific T-cell engager, that binds to DLL3 on the small cell lung cancer cell, and also to the CD3 receptor on the T cell. In turn, it activates the T cells to produce the cancer cell lysis (the breakdown of a cell caused by damage to its membrane),” Paz-Ares said during the presentation.

The primary end point of this study was objective response rate. Other end points of interest included progression-free survival (the time during and after treatment when a patient with cancer is alive without disease worsening), median duration of response (the time from when a patient first responds to treatment until disease progression or death), overall survival (the time from treatment when a patient with cancer is still alive) and treatment-emergent side effects. Follow-up was conducted for a median of 10.6 months.

Regarding baseline characteristics, the median age of patients in the 10-mg group was 64 years and 62 years in the 100-mg group. The percentage of patients who had received at least 3 prior lines of therapy was 33% and 43%, respectively, and the rate of prior anti-PD-(L)1 treatment was 73% and 70%. In both arms, the rate of DLL3 expression (a protein commonly seen in patients with SCLC) was 96%.

“There was no difference in the tumor reduction based on DLL3 expression,” Paz-Ares said. “Indeed, most patients expressed DLL3.”

The median time to objective response (or a measurable response to treatment) was 1.4 months in both groups, and the median duration of response was not reached. Of the 68 patients who responded to treatment, the duration of response was six months or longer in 40 patients (59%). Of note, 56% of the responses to treatment were ongoing at the data cutoff.

In patients treated with either the 10-mg or 100-mg dose, the median progression-free survival was 4.9 months and 3.9 months, respectively, and the median overall survival was 14.3 months and not evaluable, meaning that more than half of patients in the study were alive at the time this was assessed by researchers.

Paz-Ares noted that the overall survival data were not mature, but at the last follow-up, 57% of patients in the 10-mg group and 51% of those in the 100-mg group were still alive.

The most common treatment-emergent side effect was cytokine release syndrome, which occurred in 49% of patients in the 10-mg group and 61% of those in the 100-mg group. Of note, cytokine release syndrome is a condition that may occur after treatment with some immunotherapies, which is caused by a rapid release of cytokines in the blood and can lead to several signs and symptoms including nausea, fever, rash, headache, low blood pressure, rapid heartbeat and trouble breathing. Cytokine release syndrome primarily occurred during cycle 1 and was mostly considered grade 1 or 2. Although low, there were some instances of grade 3 cytokine release syndrome; these were reported by 5.7% of those treated with the 100-mg dose.

Treatment-emergent side effects that led to either dose interruption or reduction occurred in 14% of patients treated with the 10-mg dose and 29% in those treated with the 100-mg dose.

Immune effector cell-associated neurotoxicity syndrome (ICANS), which included associated neurologic events, occurred infrequently and were primarily observed with the 100-mg dose of tarlatamab. ICANS refers to a side effect that may occur with immunotherapy like BiTEs that related to several neurological symptoms including delirium, confusion, seizures and language difficulties. These symptoms are related to an exaggerated immune response to cancer cells that cause inflammation in the central nervous system.

“Tarlatamab represents a new immunotherapeutic approach for small-cell lung cancer, a tumor type that is characterized by an immunosuppressive microenvironment,” the researchers wrote in the simultaneous publication of the findings in The New England Journal of Medicine.

In the paper, the researchers concluded that longer follow-up of patients in this study will provide more information about the long-term durability of response to the treatment, in addition to long-term survival benefits.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.

CML Alliance
Enable registration in settings - general
Compare items
  • Total (0)
Shopping cart